pH: A major player in degenerative intervertebral disks.

Chronic lower back pain is the leading cause of disability worldwide, generating a socioeconomic cost of over $100 billion annually in the United States. Among the prominent causes of low back pain (LBP) is degeneration of the intervertebral disk (IVD), a condition known as degenerative disk disease (DDD). Despite the prevalence of DDD and multiple studies demonstrating its relationship with LBP, the mechanisms by which it contributes to pain remain unknown. Previous studies have identified potential causes for this pain, such as extracellular matrix (ECM) breakdown, changes in biomechanics, and pro-inflammatory signals. Possible pain treatments targeting these factors have been developed but with limited effects. However, low pH in DDD is a potential pain generator whose role has largely been unexplored and underappreciated. This review highlights hyperacidity's effects on the IVD, such as catabolism of disk cells and ECM, neoinnervation, altered mechanical signaling, and expression of pro-inflammatory cytokines and ion channels. This review aims to discuss what is known about the contributions of acidity to DDD pain, identify the knowledge gaps on this topic, and propose what research can be conducted to fill these gaps. We must better understand the underlying mechanisms of DDD and the interaction between hyperacidity and nociception to develop better therapeutics for this disease.